title: The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy.
abstract: Many newly discovered therapeutic agents require a delivery platform in order to translate them into clinical applications. For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assembling peptides (EAK16-II) and amino acids to minimize the use of the toxic organic solvent DMSO; hence, the biocompatibility of the PP2 nanoformulations was significantly improved. They were found to be non-hemolytic and safe for intravenous and intratracheal administration; the formulations did not alter PP2 activity in Src inhibition on cultured cells. The PP2 nanoformulation was further evaluated on a lipopolysaccharide (LPS)-induced acute lung injury mouse model. Results revealed that the pretreatment of PP2 nanoformulation could decrease the inflammatory cell infiltration and the pro-inflammatory cytokine TNF-α production in the bronchoalveolar lavage fluid after LPS stimulation. The promising therapeutic efficacy and the formulation strategy developed in this work may help further translate PP2 and other hydrophobic therapeutic agents into clinical applications.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto General Research Institute, Toronto, Ontario M5G1L7, Canada.
authors.forename: Shan-Yu
authors.initials: SY
authors.lastname: Fung
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oyaizu
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy*; D000596:Amino Acids / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000627:therapeutic use*; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C412373:AG 1879; D000596:Amino Acids; C098329:EAK16 peptide; D008070:Lipopolysaccharides; D009842:Oligopeptides; D011743:Pyrimidines